CC BY-NC-ND 4.0 · Indian J Med Paediatr Oncol 2015; 36(04): 265-270
DOI: 10.4103/0971-5851.171553

Clinical implication of thiopurine methyltransferase polymorphism in children with acute lymphoblastic leukemia: A preliminary Egyptian study

Farida H. El-Rashedy
Department of Pediatrics, Faculty of Medicine, Menoufia University, Shebeen El-Kom, Menoufia, Egypt
Seham Mohammed Ragab
Department of Pediatrics, Faculty of Medicine, Menoufia University, Shebeen El-Kom, Menoufia, Egypt
Ashraf A. Dawood
Department of Biochemistry, Faculty of Medicine, Menoufia University, Shebeen El-Kom, Menoufia, Egypt
Shaymaa A. Temraz
Department of Pediatrics, Faculty of Medicine, Menoufia University, Shebeen El-Kom, Menoufia, Egypt
› Author Affiliations
Financial support and sponsorship Nil.


Background: 6-mercaptopurine (6-MP) is an essential component of pediatric acute lymphoblastic leukemia (ALL) maintenance therapy. Individual variability in this drug-related toxicity could be attributed in part to genetic polymorphism thiopurine methyltransferase (TPMT). Aim: To investigate the frequency of common TPMT polymorphisms in a cohort of Egyptian children with ALL and the possible relation between these polymorphisms and 6-MP with short-term complications. Materials and Methods: This study included 25 children. Data related to 6-MP toxicity during the maintenance phase were collected from the patients′ files. DNA was isolated and genotyping for TPMT G460A, and A719G mutations were performed by polymerase chain reaction-restriction fragment length polymorphism. Results: Twenty (80%) of the included 25 patients had a polymorphic TPMT allele. TPMTFNx013A was the most frequent (14/25, 56%), 8 patients were homozygous and 6 were heterozygous. TPMTFNx013C mutant allele was found in 4 patients (16%) in the heterozygous state while 2 patients (8%) were found to be heterozygous for TPMTFNx013B mutant allele. TPMT mutant patients, especially homozygous, were at greater risk of 6-MP hematological toxicity without significant difference regarding hepatic toxicity. Conclusions: TPMT polymorphism was common among the studied group and was associated with increased risk of drug toxicity. A population-based multi-center study is required to confirm our results.

Publication History

Publication Date:
12 July 2021 (online)

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